Genes Required for the Fitness of Salmonella enterica Serovar Typhimurium during Infection of Immunodeficient gp91-/- phox Mice

Infection and Immunity
Andrew J GrantPietro Mastroeni

Abstract

Salmonella enterica causes systemic diseases (typhoid and paratyphoid fever), nontyphoidal septicemia (NTS), and gastroenteritis in humans and other animals worldwide. An important but underrecognized emerging infectious disease problem in sub-Saharan Africa is NTS in children and immunocompromised adults. A current goal is to identify Salmonella mutants that are not pathogenic in the absence of key components of the immune system such as might be found in immunocompromised hosts. Such attenuated strains have the potential to be used as live vaccines. We have used transposon-directed insertion site sequencing (TraDIS) to screen mutants of Salmonella enterica serovar Typhimurium for their ability to infect and grow in the tissues of wild-type and immunodeficient mice. This was to identify bacterial genes that might be deleted for the development of live attenuated vaccines that would be safer to use in situations and/or geographical areas where immunodeficiencies are prevalent. The relative fitness of each of 9,356 transposon mutants, representing mutations in 3,139 different genes, was determined in gp91(-/-) phox mice. Mutations in certain genes led to reduced fitness in both wild-type and mutant mice. To validate these result...Continue Reading

References

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Citations

Sep 30, 2017·The Journal of Antimicrobial Chemotherapy·O RossiP Mastroeni
Feb 22, 2018·MBio·Emily C A GoodallIan R Henderson
Jul 15, 2016·Clinical and Vaccine Immunology : CVI·Ellen E HigginsonSharon M Tennant
Feb 16, 2017·Scientific Reports·Bimal JanaLuca Guardabassi
Oct 31, 2019·Nucleic Acids Research·Javier Macho RendónMarc Torrent Burgas
Jun 2, 2017·BMC Genomics·Amelia R L CharbonneauAndrew S Waller
Mar 7, 2020·Proceedings of the National Academy of Sciences of the United States of America·Yara SeifBernhard O Palsson

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Datasets Mentioned

BETA
HE654726

Methods Mentioned

BETA
Illumina sequencing
PCR

Software Mentioned

Cutadapt
TraDIS
BWA mem
DESeq2
R
Covaris

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